- Email: [email protected]
976 CENTRILOBULAR CHANGES ARE KEY HISTOLOGICAL FINDINGS FOR SEGREGATING CASES OF DE NOVO AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION
POSTERS by actinomycin-D (5 mg/ml), indicating transcriptional regulation. When hepatocytes were pre-incubated for 30 min with an estrogen receptor (ER) antagonist (ICI182/780, 1 mM), induction of Mrp3 mRNA was totally abolished. Similarly, EE induced MRP3 in HepG2 cells only after transfection with ER-a. ER-a could modulate gene expression by binding to estrogen response elements (ERE), or indirectly through interaction with transcription factors such as Ap-1. An in silico analysis of MRP3 promoter region showed no presence of ERE binding sites but identified several Ap-1 binding sites. Co-transfection with plasmids encoding Ap-1 members (c-Jun plus c-Fos) and ER-a led to up-regulation of MRP3 expression (250% p < 0.05, n = 3), with no response for the ER-a (−)/Ap-1 (+) group. These results suggest involvement of up-regulation of c-Fos or c-Jun by EE in MRP3 induction, and that their interaction with ER-a is necessary. Treatment of HepG2-ER-a(+) cells with EE increased the expression of c-Jun (500%, p < 0.05, n = 3) but not c-Fos, as evaluated by western blotting of nuclear extracts. We also demonstrated by co-immunoprecipitation assays that c-Jun/ER-a interaction was increased by EE. In conclusion, EE induced Mrp3/MRP3 through a direct mechanism, requiring participation of ER-a. The increased expression of c-Jun and its further interaction with ER-a are likely involved. 974 IMMUNOLOGICAL DISEASES AS A RISK FACTOR FOR SURVIVAL IN PRIMARY SCLEROSING CHOLANGITIS: INSIGHT INTO PATHOGENESIS? C. Rupp1 , A. Mummelthei1 , P. Sauer1 , K.-H. Weiss1 , P. Schirmacher2 , A. Stiehl1 , W. Stremmel1 , D.N. Gotthardt1 . 1 Department of Medicine, 2 Institute of Pathology, University of Heidelberg, Heidelberg, Germany E-mail: [email protected] Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can be rather defined as an immune-mediated disease than an autoimmune disease. Association with other immunological diseases like inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) is well known. We evaluated the presence of immunological diseases (ID) beside IBD and AIH in a cohort of PSC patients and performed a subclassification between autoimmune (AID) and immunemediated inflammatory diseases (IMID) and report its influence on clinical outcome. Methods: Cohort study of 195 PSC patients that were evaluated over the period 1987–2010 at our tertiary care center. The presence of ID was determined by chart review. ID were sub-classified into AID and IMID, according to current guidelines. Results: 27/195 (13.8%) patients with PSC had at least one additional ID other than IBD (70%) or AIH (3%). The most frequent AIDs were autoimmune thyreopathy (2.6%) and IDDM (2.1%). The most frequent IMIDs were psoriasis (3.6%) and sarcoidosis (2.1%). After more than twenty years of follow up, PSC patients with concomitant immunological diseases had a markedly reduced actuarial transplantation-free survival rate (mean: 8.9 years vs. 16.3 years, p = 0.012). Further subgroup analysis revealed a significant reduced survival only in patients with concomitant IMID (0.017). By contrast concomitant AID showed no impact on survival. Conclusion: Concomitant immune-mediated inflammatory diseases but not autoimmune diseases represent an independent risk factor for reduced transplantation-free survival in patients with PSC. These findings might point to a new subgroup of patients with a more serious phenotype of PSC.
975 INTERACTIONS AMONG LIVER INFILTRATED CTL, TREG AND NKT CELL FROM SPLEEN PARTICIPATED IN THE PATHOGENESIS OF EXPERIMENTAL AUTOIMMUNE HEPATITIS C. Saeki, H. Takahashi, K. Takano, R. Nakagawa, M. Nakano, S. Honma, M. Zeniya. Gastroenterology and Hepatology, Jikei University School of Medicine, Tokyo, Japan E-mail: [email protected] Background and Aims: Cytotoxic T cell (CTL) and regulatory T cell (Treg) may participate in the pathogenesis of autoimmune hepatitis (AIH). However, the mechanism of their intrahepatic infiltration remains unknown. The pathological role of NKT cell in AIH is not clear either. We analyzed the quality and quantity of intrahepatic and splenic CTL, Treg and NKT cell in AIH model which we previously established to reveal their role in the pathogenesis of AIH. Methods: AIH model was made by vaccination of fusion cell (FC) of dendritic cells and well differentiated hepatoma cells (Hepa1–6) followed by administration of IL-12. Hepatocyte specific CTL was induced in this model and intrahepatic inflammation peaked on day 21 followed by decrease on day 23 after FC vaccination. The numbers of intrahepatic and splenic CTL, Treg and NKT cell were measured by FACS. The expression of CXCR3 on CTL and Treg was evaluated by FACS and intrahepatic mRNA expression of CXCL9 was evaluated by qRT-PCR. Inhibitory activity of intrahepatic Treg against effecter T cells was assessed using thymidine incorporation method. To analyze the role of NKT cell, a-GalCer was injected to FC treated mice and intrahepatic CTL infiltration was assessed 48 hours after a-GalCer administration. Results: Intrahepatic CXCR3 positive CTL and Treg were increased on day 21 and decreased on day 23. Intrahepatic expression of CXCL9 was also up-regulated on day 21. On the contrary, splenic CTL and Treg were decreased on day 21. Accumulated Treg suppressed the proliferation of effecter T cells in a dose-dependent manner. Intrahepatic IFN-g producing NKT cell increased on day 21. Intrahepatic inflammation was attenuated in CD1d KO mice. a-GalCer administration induced severe hepatic inflammation with abundant intrahepatic CTL infiltration. Conclusion: Both CTL and Treg recruited into the inflamed liver from spleen by using CXCR3/CXCL9 pathway. NKT cell enhanced hepatic inflammation by inducing CTL recruitment into the liver. On the other hand, intrahepatic accumulated Treg may participate in the natural occurring recovery in this model. These results indicated that both effecter and regulatory cell infiltrate inflamed liver from spleen and influence each other to participate in the pathogenesis of AIH. 976 CENTRILOBULAR CHANGES ARE KEY HISTOLOGICAL FINDINGS FOR SEGREGATING CASES OF DE NOVO AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION M. Sebagh1,2,3 , A. Coilly4 , M. Castillo-Rama5 , A. Dos Santos2,3 , V. Delvart4 , C. Johanet6 , A.-M. Roque-Afonso2,3,7 , B. Roche4 , J.-C. Duclos-Vallee2,3,4 , D. Azoulay4 , D. Samuel2,3,4 , A.-J. Demetris5 . 1 Laboratoire Anatomie Pathologique, AP-HP – Hˆ opital Paul Brousse, 2 Unit 785, INSERM, 3 UMR-S785, Univ Paris-Sud, 4 Centre Hepato-Biliaire, AP-HP – Hˆ opital Paul Brousse, Villejuif, France, 5 Division of Transplantation, University of Pittsburgh Medical Center, Pittsburg, PA, USA, 6 Service Immunologie et Hematologie Biologiques, AP-HP – Hˆ opital Saint Antoine, Paris, 7 Laboratoire de Virologie, AP-HP – Hˆ opital Paul Brousse, Villejuif, France E-mail: [email protected] Introduction: De novo auto-immune hepatitis (AIH) after liver transplantation is histologically defined as a hepatitic pattern of injury, characterized by lymphoplasmacytic inflammation with necro-inflammatory activity comparable to AIH in native liver.
Journal of Hepatology 2012 vol. 56 | S225–S388
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POSTERS However, this general definition is difficult to apply in practice because specific histological criteria are not clearly delineated. The aim of this study was to determine which histological features best correlated with clinical and serological features ofAIH. Patients: Index liver biopsies with auto-immune-like hepatitis from 2 independent centres (Villejuif, N = 35 and UPMC, N = 20) were reviewed. Patients transplanted for AIH were excluded. Significant histological features were correlated with the diagnosis of de novo AIH based on a complete retrospective review of the clinical and serological data, including response to treatment. Results: A diagnosis of new onset AIH was assigned to 24/35 (68%) and 17/20 (85%) patients. The ratio of plasma cells in the portal and centrilobular infiltrate, and the topography of the necroinflammatory activity were discriminate in univariate analysis. Results were optimized when centrilobular necro-inflammatory activity (p = 0.04) and centrilobular plasma cell ratio of 30–50% (p = 0.05) were combined (in multivariate analysis applied to the global population). Conclusion: This histological pattern of injury correlated with clinical and biological data measures of autoimmunity in liver recipients. It can be used to segregate such cases for further study and included in international scoring systems when applied in the context of liver transplantation. 977 CLINICOPATHOLOGICAL FEATURES AND OUTCOME OF AUTOIMMUNE HEPATITIS/PRIMARY SCLEROSING CHOLANGITIS OVERLAP SYNDROME I. Simionov, L. Gheorghe. Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania E-mail: [email protected] Background: Overlap Syndrome between Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC) is not well characterised in adults, being a relatively uncommon disease. Aim: To characterise and evaluate the natural history of patients with AIH/PSC overlap Syndrome, compared with patients with “classical” PSC. Patients and Method: We included 55 PSC patients followed for at least three years, with at least three admissions in our unit, 8 were diagnosed withAIH/PSC overlap syndrome(4 simultaneous and 4 succesive OLS, in 2 cases AIH was first featured and in 2 PSC). Patients with OLS received immunosupressive treatment and UDCA, those with PSC only UDCA. Results: The OLS group significantly differed from PSC group in: percent of female gender (87.5% vs 29.79%, p = 0.011), mean AST (259.25±94.5 vs 124.04±60.797, p = 0.0005), mean ALT (367.38±121.114 vs 176.32±81.345, p = 0.0002), mean IgG (3571.13±672.963 vs 2681.04±802.689, p = 0.005) and IgM (405.38±113.431 vs 254.19±111.374, p = 0.001), cholesterol level (195.28±60.665 vs 238.88±46.416, p = 0.05), plasmocytes on liver histology (75% vs 29%, p = 0.02), ANA positive >1:80 (62.5% vs 12.8%, p = 0.002) and percent of patients with “definite AIH”diagnosis according to IAHG score (37.5% vs 0%, p = 0.001). There were not statistically significant differences between our groups in next parameters: patients age at diagnosis (35.11+ 11.42 vs 33.87 + 10.304, p = 0.412), IBD association (25% vs 59.57%, p = 0.07), “onionskin” fibrosis on liver histology (50% vs 32.25%, p = 0.208), ASMA positivity (75% vs 38.3%, p = 0.06), pANCA positivity (62.5% vs 63.8%, p = 0.617). Athough Mayo risk score for PSC was initially higher in OLS groupe (p = 0.174), it decreased in OLS, while it increased in PSC group during follow-up (p = 0.434). The major events during followup were: liver transplantation (3in OLS group, 1 in PSC group), malignancies(8 in PSC, 0 in OLS), death(5 PSC, 0 OLS). KaplanMeyer survival curves showed no significant differences between OLS and PSC group, although it was longer in OLS patients. S382
Conclusions: AIH/PSC OLS in not very rare in clinical practice. We have to think about it in AIH patients who became unresponsive to immunosuppressive therapy or in a CSP patient with flares of aminotransferases. Prognosis in OLS seems to be better that in classical PSC. 978 PLATELET FUNCTION IN PATIENTS WITH EARLY PRIMARY BILIARY CIRRHOSIS ESTIMATED BY ROTEM THROMBOELASTOGRAPHY AND FLOW CYTOMETRY. COMPARISON WITH HEALTHY CONTROLS I. Binas1 , J. Vlachogiannakos1 , P. Kotsi2 , I. Anastasopoulou2 , I. Vafiadi-Zoumbouli1 , S.D. Ladas1 . 1 Hepatogastroenterology Unit, First Department of Medicine Propaedeutic, Medical School, Athens University, Laikon General Hospital, 2 Blood Transfusion Center, Haemophilia Center, Laikon General Hospital, Athens, Greece E-mail: [email protected] Background and Aims: Previous studies have found that PBC patients with advanced disease are hypercoagulable with no thrombophilic factors as compared to non-cholestatic cirrhotics. We investigated if hypercoagulability is present in early stage PBC. Methods: Twenty five newly diagnosed PBC patients with early disease (mean age:57.3±12, stage 1 or 2 by Scheuer classification, mean bilirubin:0.8±0.3, no evidence of portal hypertension) and 25 healthy controls matched by gender and age (±5 years). PBC patients and controls were evaluated with Rotem (Natem) Thromboelastography (TEG), platelet aggregation, PT, APTT, fibrinogen and LFTs. Four TEG parameters were evaluated (CT, CFT, alpha angle and MCF). Platelet aggregation was determined as maximal change of light transmission after the addition of ADP, collagen and epinephrine. Flow cytometry was used to evaluate the expression of GPIIb, GPIIa and P-Selectin on platelets’ surface. The investigators who performed the experiments were unaware of the source of each sample (PBC patient or control). Hypercoagulability defined by values >2SD over healthy controls. Results: TEG parameters were within normal range in all 25 PBC patients. Mean (±SD) values did not differ significantly in PBC patients as compared to controls (CT: 509±107 vs. 483±104, p = 0.346; CFT: 116±44 vs. 133±48, p = 0.209; alpha angle: 64.9±5.7 vs. 65.3±7.5, p = 0.903; MCF: 63±7 vs. 64±8.6, p = 0.689). PT and APTT were not significantly different between PBC and controls (p=NS). PT was significantly correlated with CT values (p = 0.005). No correlation was found between MCF and bilirubin (p = 0.114) neither with albumin (p = 0.235). Platelet aggregation in PBC patients was not significantly different from controls (ADP 2.5 mM: 70±26 vs. 62±25, p = 0.223; ADP 5 mM: 77±18 vs. 78±20, p = 0.910; Collagen: 73.3±13 vs. 66±18, p = 0.123; Epinephrine: 79±17 vs. 72±24, p = 0.201). Although the expression of GPIIb, GPIIIa and P-Selectin were within normal range in PBC patients, GPIIb and P-selectin expression was increased as compared to the control group and the difference was statistically significant (p = 0.005 and p = 0.006 respectively). Conclusions: We could not detect hypercoagulability in our cohort of patients with early PBC. However, the increased expression of GPIIb and P-Selectin on their platelets surface may have important clinical implications and merits further investigation. 979 SECONDARY SCLEROSING CHOLANGITIS IN CRITICALLY ILL PATIENTS: WHO IS AT RISK AND HOW TO DIMINISH IT 1 T. Voigtlander ¨ , A.A. Negm1 , A.S. Schneider1 , M.P. Manns1 , J. Wedemeyer1,2 , T.O. Lankisch1 . 1 Medical School Hannover, Hannover, 2 Medical Department I, Robert Koch Hospital Gehrden, Gehrden, Germany E-mail: [email protected] Introduction: Secondary sclerosing cholangitis (SSC) in critically ill patients (SSC-CIP) is an under-diagnosed emerging disease entity.
Journal of Hepatology 2012 vol. 56 | S225–S388
975 INTERACTIONS AMONG LIVER INFILTRATED CTL, TREG AND NKT CELL FROM SPLEEN PARTICIPATED IN THE PATHOGENESIS OF EXPERIMENTAL AUTOIMMUNE HEPATITIS C. Saeki, H. Takahashi, K. Takano, R. Nakagawa, M. Nakano, S. Honma, M. Zeniya. Gastroenterology and Hepatology, Jikei University School of Medicine, Tokyo, Japan E-mail: [email protected] Background and Aims: Cytotoxic T cell (CTL) and regulatory T cell (Treg) may participate in the pathogenesis of autoimmune hepatitis (AIH). However, the mechanism of their intrahepatic infiltration remains unknown. The pathological role of NKT cell in AIH is not clear either. We analyzed the quality and quantity of intrahepatic and splenic CTL, Treg and NKT cell in AIH model which we previously established to reveal their role in the pathogenesis of AIH. Methods: AIH model was made by vaccination of fusion cell (FC) of dendritic cells and well differentiated hepatoma cells (Hepa1–6) followed by administration of IL-12. Hepatocyte specific CTL was induced in this model and intrahepatic inflammation peaked on day 21 followed by decrease on day 23 after FC vaccination. The numbers of intrahepatic and splenic CTL, Treg and NKT cell were measured by FACS. The expression of CXCR3 on CTL and Treg was evaluated by FACS and intrahepatic mRNA expression of CXCL9 was evaluated by qRT-PCR. Inhibitory activity of intrahepatic Treg against effecter T cells was assessed using thymidine incorporation method. To analyze the role of NKT cell, a-GalCer was injected to FC treated mice and intrahepatic CTL infiltration was assessed 48 hours after a-GalCer administration. Results: Intrahepatic CXCR3 positive CTL and Treg were increased on day 21 and decreased on day 23. Intrahepatic expression of CXCL9 was also up-regulated on day 21. On the contrary, splenic CTL and Treg were decreased on day 21. Accumulated Treg suppressed the proliferation of effecter T cells in a dose-dependent manner. Intrahepatic IFN-g producing NKT cell increased on day 21. Intrahepatic inflammation was attenuated in CD1d KO mice. a-GalCer administration induced severe hepatic inflammation with abundant intrahepatic CTL infiltration. Conclusion: Both CTL and Treg recruited into the inflamed liver from spleen by using CXCR3/CXCL9 pathway. NKT cell enhanced hepatic inflammation by inducing CTL recruitment into the liver. On the other hand, intrahepatic accumulated Treg may participate in the natural occurring recovery in this model. These results indicated that both effecter and regulatory cell infiltrate inflamed liver from spleen and influence each other to participate in the pathogenesis of AIH. 976 CENTRILOBULAR CHANGES ARE KEY HISTOLOGICAL FINDINGS FOR SEGREGATING CASES OF DE NOVO AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION M. Sebagh1,2,3 , A. Coilly4 , M. Castillo-Rama5 , A. Dos Santos2,3 , V. Delvart4 , C. Johanet6 , A.-M. Roque-Afonso2,3,7 , B. Roche4 , J.-C. Duclos-Vallee2,3,4 , D. Azoulay4 , D. Samuel2,3,4 , A.-J. Demetris5 . 1 Laboratoire Anatomie Pathologique, AP-HP – Hˆ opital Paul Brousse, 2 Unit 785, INSERM, 3 UMR-S785, Univ Paris-Sud, 4 Centre Hepato-Biliaire, AP-HP – Hˆ opital Paul Brousse, Villejuif, France, 5 Division of Transplantation, University of Pittsburgh Medical Center, Pittsburg, PA, USA, 6 Service Immunologie et Hematologie Biologiques, AP-HP – Hˆ opital Saint Antoine, Paris, 7 Laboratoire de Virologie, AP-HP – Hˆ opital Paul Brousse, Villejuif, France E-mail: [email protected] Introduction: De novo auto-immune hepatitis (AIH) after liver transplantation is histologically defined as a hepatitic pattern of injury, characterized by lymphoplasmacytic inflammation with necro-inflammatory activity comparable to AIH in native liver.
Journal of Hepatology 2012 vol. 56 | S225–S388
S381
POSTERS However, this general definition is difficult to apply in practice because specific histological criteria are not clearly delineated. The aim of this study was to determine which histological features best correlated with clinical and serological features ofAIH. Patients: Index liver biopsies with auto-immune-like hepatitis from 2 independent centres (Villejuif, N = 35 and UPMC, N = 20) were reviewed. Patients transplanted for AIH were excluded. Significant histological features were correlated with the diagnosis of de novo AIH based on a complete retrospective review of the clinical and serological data, including response to treatment. Results: A diagnosis of new onset AIH was assigned to 24/35 (68%) and 17/20 (85%) patients. The ratio of plasma cells in the portal and centrilobular infiltrate, and the topography of the necroinflammatory activity were discriminate in univariate analysis. Results were optimized when centrilobular necro-inflammatory activity (p = 0.04) and centrilobular plasma cell ratio of 30–50% (p = 0.05) were combined (in multivariate analysis applied to the global population). Conclusion: This histological pattern of injury correlated with clinical and biological data measures of autoimmunity in liver recipients. It can be used to segregate such cases for further study and included in international scoring systems when applied in the context of liver transplantation. 977 CLINICOPATHOLOGICAL FEATURES AND OUTCOME OF AUTOIMMUNE HEPATITIS/PRIMARY SCLEROSING CHOLANGITIS OVERLAP SYNDROME I. Simionov, L. Gheorghe. Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania E-mail: [email protected] Background: Overlap Syndrome between Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC) is not well characterised in adults, being a relatively uncommon disease. Aim: To characterise and evaluate the natural history of patients with AIH/PSC overlap Syndrome, compared with patients with “classical” PSC. Patients and Method: We included 55 PSC patients followed for at least three years, with at least three admissions in our unit, 8 were diagnosed withAIH/PSC overlap syndrome(4 simultaneous and 4 succesive OLS, in 2 cases AIH was first featured and in 2 PSC). Patients with OLS received immunosupressive treatment and UDCA, those with PSC only UDCA. Results: The OLS group significantly differed from PSC group in: percent of female gender (87.5% vs 29.79%, p = 0.011), mean AST (259.25±94.5 vs 124.04±60.797, p = 0.0005), mean ALT (367.38±121.114 vs 176.32±81.345, p = 0.0002), mean IgG (3571.13±672.963 vs 2681.04±802.689, p = 0.005) and IgM (405.38±113.431 vs 254.19±111.374, p = 0.001), cholesterol level (195.28±60.665 vs 238.88±46.416, p = 0.05), plasmocytes on liver histology (75% vs 29%, p = 0.02), ANA positive >1:80 (62.5% vs 12.8%, p = 0.002) and percent of patients with “definite AIH”diagnosis according to IAHG score (37.5% vs 0%, p = 0.001). There were not statistically significant differences between our groups in next parameters: patients age at diagnosis (35.11+ 11.42 vs 33.87 + 10.304, p = 0.412), IBD association (25% vs 59.57%, p = 0.07), “onionskin” fibrosis on liver histology (50% vs 32.25%, p = 0.208), ASMA positivity (75% vs 38.3%, p = 0.06), pANCA positivity (62.5% vs 63.8%, p = 0.617). Athough Mayo risk score for PSC was initially higher in OLS groupe (p = 0.174), it decreased in OLS, while it increased in PSC group during follow-up (p = 0.434). The major events during followup were: liver transplantation (3in OLS group, 1 in PSC group), malignancies(8 in PSC, 0 in OLS), death(5 PSC, 0 OLS). KaplanMeyer survival curves showed no significant differences between OLS and PSC group, although it was longer in OLS patients. S382
Conclusions: AIH/PSC OLS in not very rare in clinical practice. We have to think about it in AIH patients who became unresponsive to immunosuppressive therapy or in a CSP patient with flares of aminotransferases. Prognosis in OLS seems to be better that in classical PSC. 978 PLATELET FUNCTION IN PATIENTS WITH EARLY PRIMARY BILIARY CIRRHOSIS ESTIMATED BY ROTEM THROMBOELASTOGRAPHY AND FLOW CYTOMETRY. COMPARISON WITH HEALTHY CONTROLS I. Binas1 , J. Vlachogiannakos1 , P. Kotsi2 , I. Anastasopoulou2 , I. Vafiadi-Zoumbouli1 , S.D. Ladas1 . 1 Hepatogastroenterology Unit, First Department of Medicine Propaedeutic, Medical School, Athens University, Laikon General Hospital, 2 Blood Transfusion Center, Haemophilia Center, Laikon General Hospital, Athens, Greece E-mail: [email protected] Background and Aims: Previous studies have found that PBC patients with advanced disease are hypercoagulable with no thrombophilic factors as compared to non-cholestatic cirrhotics. We investigated if hypercoagulability is present in early stage PBC. Methods: Twenty five newly diagnosed PBC patients with early disease (mean age:57.3±12, stage 1 or 2 by Scheuer classification, mean bilirubin:0.8±0.3, no evidence of portal hypertension) and 25 healthy controls matched by gender and age (±5 years). PBC patients and controls were evaluated with Rotem (Natem) Thromboelastography (TEG), platelet aggregation, PT, APTT, fibrinogen and LFTs. Four TEG parameters were evaluated (CT, CFT, alpha angle and MCF). Platelet aggregation was determined as maximal change of light transmission after the addition of ADP, collagen and epinephrine. Flow cytometry was used to evaluate the expression of GPIIb, GPIIa and P-Selectin on platelets’ surface. The investigators who performed the experiments were unaware of the source of each sample (PBC patient or control). Hypercoagulability defined by values >2SD over healthy controls. Results: TEG parameters were within normal range in all 25 PBC patients. Mean (±SD) values did not differ significantly in PBC patients as compared to controls (CT: 509±107 vs. 483±104, p = 0.346; CFT: 116±44 vs. 133±48, p = 0.209; alpha angle: 64.9±5.7 vs. 65.3±7.5, p = 0.903; MCF: 63±7 vs. 64±8.6, p = 0.689). PT and APTT were not significantly different between PBC and controls (p=NS). PT was significantly correlated with CT values (p = 0.005). No correlation was found between MCF and bilirubin (p = 0.114) neither with albumin (p = 0.235). Platelet aggregation in PBC patients was not significantly different from controls (ADP 2.5 mM: 70±26 vs. 62±25, p = 0.223; ADP 5 mM: 77±18 vs. 78±20, p = 0.910; Collagen: 73.3±13 vs. 66±18, p = 0.123; Epinephrine: 79±17 vs. 72±24, p = 0.201). Although the expression of GPIIb, GPIIIa and P-Selectin were within normal range in PBC patients, GPIIb and P-selectin expression was increased as compared to the control group and the difference was statistically significant (p = 0.005 and p = 0.006 respectively). Conclusions: We could not detect hypercoagulability in our cohort of patients with early PBC. However, the increased expression of GPIIb and P-Selectin on their platelets surface may have important clinical implications and merits further investigation. 979 SECONDARY SCLEROSING CHOLANGITIS IN CRITICALLY ILL PATIENTS: WHO IS AT RISK AND HOW TO DIMINISH IT 1 T. Voigtlander ¨ , A.A. Negm1 , A.S. Schneider1 , M.P. Manns1 , J. Wedemeyer1,2 , T.O. Lankisch1 . 1 Medical School Hannover, Hannover, 2 Medical Department I, Robert Koch Hospital Gehrden, Gehrden, Germany E-mail: [email protected] Introduction: Secondary sclerosing cholangitis (SSC) in critically ill patients (SSC-CIP) is an under-diagnosed emerging disease entity.
Journal of Hepatology 2012 vol. 56 | S225–S388